Picolinic acid → Diethyl 2-(5-bromopyridin-2-yl)malonate

HRID 220200

反応式

HRID 220200 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[N:6][CH:7]=1.[CH2:9]([O:11][C:12](=[O:19])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10].C([O-])([O-])=O.[Cs+].[Cs+].N1C=CC=CC=1C(O)=O>O1CCOCC1.[Cu]I>[CH2:9]([O:11][C:12](=[O:19])[CH:13]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10]

参加物

7

反応物 4

HCID 1018Picolinic acidHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 5936905-Bromo-2-iodopyridine

生成物 1

HCID 59238270Diethyl 2-(5-bromopyridin-2-yl)malonate収率 50%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 5-bromo-2-iodo-pyridine (56.8 g, 0.2 mol), malonic acid diethyl ester (64 g, 0.4 mol), CuI (3.8 g, 0.02 mol), Cs2CO3 (195.5 g, 0.6 mol) and pyridine-2-carboxylic acid (2.46 g, 0.04 mol) in 1,4-dioxane (400 mL) was stirred at 70 degrees Celsius under N2 for 24 hours. After cooling to room temperature, the solid was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate (400 mL) and washed with water, brine, dried over Na2SO4, filtered, concentrated in vacuo, the crude product was purified by flash chromatography (Petroleum Ether:EtOAc=20:1) to obtain an oil (31.6 g, 50%). MS: calc'd 316 (MH+), exp 316 (MH+). 1H NMR (d6-DMSO, 400 MHz), 8.68 (d, 1H, J=2.4 Hz), 8.11 (dd, 1H, J=2.4, 8.4 Hz), 7.45 (d, 1H, J=8.4 Hz), 5.16 (s, 1H), 4.20-4.07 (m, 4H), 1.18 (t, J=8.4 Hz, 6H).

後処理

  1. filtrationthe solid was filtered
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in ethyl acetate (400 mL)
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude product was purified by flash chromatography (Petroleum Ether:EtOAc=20:1)

出典と根拠

ORDレコード
ord-a0f0e68cae3740dab0a1c7d2c66551dc
出典データセット
uspto-grants-2012_06
特許番号
US08202866B2

関連ノート

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